rs17258746

Positions:

• chr1-207079302-T-A
• chr1-207079302-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367079.3(PFKFB2):​c.*283T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 518,216 control chromosomes in the GnomAD database, including 4,286 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1089 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3197 hom.)
• Consequence: PFKFB2 ENST00000367079.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

PFKFB2 (HGNC:8873): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2) The protein encoded by this gene is involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKFB2	NM_001018053.2	c.*283T>A		3_prime_UTR_variant	15/15
PFKFB2	XM_024447657.2	c.*283T>A		3_prime_UTR_variant	15/15
PFKFB2	XM_047422549.1	c.*283T>A		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKFB2	ENST00000367079.3	c.*283T>A		3_prime_UTR_variant	15/15	1		P1
PFKFB2	ENST00000473310.5	n.519T>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17336 AN: 152132 Hom.: 1087 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.129 AC: 47386 AN: 365966 Hom.: 3197 Cov.: 0 AF XY: 0.129 AC XY: 24772 AN XY: 192598

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.114 AC: 17338 AN: 152250 Hom.: 1089 Cov.: 32 AF XY: 0.115 AC XY: 8550 AN XY: 74440

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0902

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0640 Hom.: 65

Bravo AF: 0.112

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17258746; hg19: chr1-207252647;